CpG DNA rescues B cells from apoptosis by activating NFκB and preventing mitochondrial membrane potential disruption via a chloroquine sensitive pathway

Isolated murine splenic a cells gradually undergo spontaneous apoptosis while WEHI-231 a lymphoma cells undergo activation-induced apoptosis, Unmethylated CpG dinucleotides in a particular sequence context (CpG motif) in bacterial DNA or in synthetic oligodeoxynucleotides (CpG DNA) rescue both splenic a cells and WEHI-231 cells from apoptosis, an effect which could potentially contribute to autoimmune disease. Chloroquine has; been used as an effective therapeutic agent for some autoimmune diseases, although the mechanism of action is riot clearly understood. Low concentrations of chloroquine (<5 mu M) selectively abolished CpG DNA-mediated protection against spontaneous apoptosis of splenic a cells and against anti-IgM-induced apoptosis of WEHI-231 cells without affecting anti-apoptotic activities of anti-CD40 or lipopolsaccharide. CpG DNA effectively prevented mitochondrial membrane potential disruption through a chloroquine-sensitive pathway in splenic B cells, Apoptosis protection by CpG DNA was also associated with increased expression of several proto-oncogenes and oncoproteins directly and/or indirectly through a rapid and sustained activation of NF kappa B in splenic a cells and WEHI-231 cells, These effects were also suppressed by chloroquine, Our results suggest that despite the difference in maturation phenotype of splenic a cells and WEHI-231 cells, CpG DNA rescues both from apoptosis by similar pathway, which is blocked at an early step by chloroquine.